FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-1alpha in the Presence of 27-hydroxycholesterol.
10.4196/kjpp.2014.18.6.475
- Author:
Weon HEO
1
;
Sun Mi KIM
;
Seong Kug EO
;
Byung Yong RHIM
;
Koanhoi KIM
Author Information
1. Department of Pharmacology, Pusan National University School of Medicine, Yangsan, 626-870, Korea. koanhoi@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
27-Hydroxycholesterol;
Interleukin-1;
Monocytes/macrophages;
TLR-6
- MeSH:
Cholesterol;
Cytokines;
Inflammation;
Interleukin-1;
Interleukin-1alpha*;
Toll-Like Receptors*
- From:The Korean Journal of Physiology and Pharmacology
2014;18(6):475-480
- CountryRepublic of Korea
- Language:English
-
Abstract:
We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the IL-1alpha gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of IL-1alpha . Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and IL-1alpha. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and IL-1alpha induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of IL-1alpha . These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of IL-1alpha in monocytic cells via multiple signaling pathways.
